Therapy - immunomodulation - Part IIFriday, September 30, 2005, 15:30 - 17:00
A phase II study of oral ovine interferon tau in clinically isolated syndromes or relapsing-remitting MSE. Waubant, G. Buckle, N. Kachuck, D. Bourdette, D. Gilman, L. Villarete, C. Liu, J. Sharma, S. Egovora, R. Bakshi, C. Guttman, H. Weiner (San Francisco, Boston, Los Angeles, Portland, Reno, Alameda, USA)
Objective: One of the primary objectives is to determine if oral recombinant ovine interferon tau (IFNtau) is well tolerated in patients with clinically isolated syndromes (CIS) or relapsing-remitting (RRMS).
Background: IFNtau, a type I IFN, is a pregnancy recognition hormone in ruminants that has antiviral properties. IFNtau induces secretion of IL-10, and suppresses IFNgamma-inducible class II upregulation on antigen presenting cells. IFNtau prevents EAE when given orally or parenterally. IFNtau has a specific antiviral activity of 2- 4 x 108 units per mg protein. In contrast to other type I IFNs, no toxicity of IFNtau was observed in a phase I MS clinical trial. Mild asthenia and headaches have been reported at the dose of 9 mg per day in patients with hepatitis C.
Design/methods: This is a multicenter, open-label phase II study in 40 patients with CIS or RRMS naïve or intolerant to IFN therapy who have received no IV steroids for at least 30 days and no glatiramer acetate for at least 90 days before first MRI scan. During the pre-treatment phase, patients undergo 3-monthly enhanced brain MRI scans. If patients display at least one Gd+ lesion on one of these 3 MRI scans, they start the treatment phase (oral IFNtau 3 mg tid for 9 months) and undergo monthly MRI scans, physical and EDSS evaluations, and laboratory and cytokine measures for 9 months. Then, all patients will discontinue IFNtau and will be evaluated in a 3 month post-treatment phase and will undergo a last brain MRI scan at month 12. The number of on-treatment new Gd+ lesions will be compared to pre-treatment and post-treatment.
Results: A total of 28 patients have been screened. Two patients are still in the pre-treatment phase. The mean age at entry in the study is 41.3 years. The sex ratio is two females to one male. Sixteen of 25 patients (64%) who completed 3 pre-treatment scans have demonstrated Gd+. Mean monthly number of Gd+ lesions during screening was 2 ± 1.6. Fifteen patients have been on oral IFNtau for an average period of 3 months. At this time, no serious adverse event (AE) has been reported. No patient has discontinued treatment because of AE. Most AE were reported as mild or moderate. The most frequently reported AE was musculoskeletal discomfort (aches, pain or stiffness).
Conclusions: Oral IFNtau also known as Tauferon™ is an interesting promising agent for MS as it is orally administered and is well tolerated. Screening data collected in this study is very important for the design of future similar studies.